Our studies continue to pursue questions relating to the interactions of DNA and cell during the process of transformation of Haemophilus. A major question concerns the specificity of interaction between Haemophilus cells and DNA in solution. It has now been shown that this specificity can be very strict for double-stranded DNA, on the other hand, single-stranded DNA is bound irrespective of its origin. Double-stranded DNA from non-Haemophilus strains can be bound if it is joined to Haemophilus DNA. In ability to be foreign DNA is not due to extensive nuclease activity, but rather a lack of recognition of a receptor. Plasmid transformation that usually occurs with a frequency of 10 to the minus 6th power to 10 to the minus 7th power in H. parainfluenzae has been improved by the development of a new procedure for preparing competent cells. Transformation of an ampicillin plasmid is increased about 1000 fold. Mutants deficient in competence have been isolated from H. parainfluenzae. They differentiate between plasmid transfection, phage transfection, and transformation. These data suggest that plasmid transfection utilizes at least part of the pathway for chromosomal transformation but the processes differ in complexity or specific requirements. Pili associated with H. parainfluenzae appears to be required for agglutination by red blood cells, as demonstrated by the isolation of mutants without pili that are non-agglutinable, however, these cells transform with normal efficiency. Procedures have been developed to isolate bacterial structures that are associated with DNA binding.